Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals

2015 ◽  
Vol 15 (7) ◽  
pp. 869-880 ◽  
Author(s):  
Donna M Roscoe ◽  
Yun-Fu Hu ◽  
Reena Philip
Keyword(s):  
Companion Diagnostics ◽  
Regulatory Perspective ◽  
Companion Diagnostic

A systematic approach to companion diagnostic development: A case study for omacetaxine (OM) for the treatment of chronic myelogenous leukemia (CML).

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 100-100
Author(s):  
Carol L. Preisig
Keyword(s):  
Systematic Approach ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Myelogenous Leukemia ◽  
Translational Bioinformatics ◽  
Stratified Medicine ◽  
Companion Diagnostics ◽  
Trade Offs ◽  
Companion Diagnostic ◽  
The Impact

100 Background: In the age of genomically informed medicine, therapeutic development carries with it the imperative to employ genomics in patient selection. Physicians expect genomics-based methods to identify treatments likely to be effective, and identify anomalies likely to cause adverse response for a given patient. Companion diagnostics should support such rule-in and rule-out decisions. We demonstrate a systematic approach to companion diagnostics that leverages new methods in translational bioinformatics and clinical economics. CML therapies have been at the forefront of genomically informed medicine. Early TKI inhibitors targeting the BCR-ABL fusion protein are highly effective. With time, however, they induce resistance-creating mutations in many patients. Omacetixine, a translation inhibitor, was expected to help this CML patient subpopulation which has few therapeutic alternatives. We use this well-characterized drug and publicly available data to demonstrate a prospective approach to companion diagnostics. Methods: We used translational bioinformatics, incorporating pathway, cell line, and patient data to identify biologically plausible biomarkers from which alternative companion diagnostic paths were constructed. These alternatives were analyzed using a modified version of the MIT Stratified Medicine Model to assess the clinical economics of each path. Results: From a systematic look at the biology of the disease, the unique mechanism of action of OM and the clinical need, we identified 3 alternative companion diagnostics for OM. Economic analyses quantified the trade-offs of targeting different subpopulations for the indication, clarifying the impact of biomarker selection based on clinical need or biology. Other analyses have shown that eNPV can be halved or doubled based on strategy choice. Conclusions: Combining applied translational bioinformatics and stratified medicine economics provides an effective approach to companion diagnostic selection. This approach can reduce drug-development cost and clinical risk while providing physicians with better genomics-based methods for clinical decision-making.

Association of gene expression module biomarkers with clinical and therapeutic endpoints and their use with a universal companion diagnostic assay.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 228-228
Author(s):  
S. A. Tomlins ◽  
P. Williams ◽  
S. Sadis ◽  
P. Wyngaard ◽  
K. Oades ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Response To Therapy ◽  
Clinical Samples ◽  
Molecular Heterogeneity ◽  
Diagnostic Assay ◽  
Companion Diagnostics ◽  
Genomic Signatures ◽  
Companion Diagnostic

228 Background: Gene expression patterns are increasingly capable of stratifying patients based on prognosis and response to therapy. Given the limited availability of sample tissue, however, it is not feasible to utilize every test for every patient, suggesting the need for a universal companion diagnostic assay that is informative with respect to multiple clinical and therapeutic endpoints. Key challenges are identification of appropriate gene expression biomarkers, translation of biomarkers to clinical assays, and development of reliable gene expression profiling of formalin-fixed clinical specimens. Here we describe a novel RT-PCR biomarker assay optimized for FFPE clinical samples that has broad prognostic and predictive potential. Methods: A co-expression meta-analysis of 5,339 breast tumors from 56 microarray datasets identified highly co-expressed sets of genes (modules) across multiple datasets. Module biomarkers were tested for their ability to associate with prognostic and predictive targets in published datasets. In addition, each module was reduced from 10–1000 genes to 2-3 genes for use in companion diagnostic assays based on degree of co-expression across the meta-analysis, and validated against an independent panel of tumor samples. Results: This study demonstrates that a single test utilizing multiple module biomarkers is informative with respect to standard parameters such as ER, PR and Her2, and in addition reproduces existing prognostic and predictive genomic signatures. Furthermore, we show that modules of 10-1000 genes can be represented by 2-3 genes for direct use in companion diagnostics development. Conclusions: The molecular heterogeneity of breast cancer can be summarized by discrete gene expression modules that individually represent distinct biological programs, and that collectively can be represented by as few as 96 genes. Modules, together with outlier genes, allow for summation of the entire transcriptional program and provide a universal assay with broad application to companion diagnostics development.

Avenues to Precision Oncology

2020 ◽  
pp. 36-45
Author(s):  
Alexander Meisel
Keyword(s):  
Precision Medicine ◽  
Trial Design ◽  
Ad Hoc ◽  
Molecular Targets ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
Companion Diagnostics ◽  
Bona Fide ◽  
The One

Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.

Policy Recommendations to Reduce Toxic Exposures for Nail Salon Workers

2011 ◽  
Vol 9 (1-2) ◽  
pp. 43-50 ◽  
Author(s):  
Julia Liou ◽  
Catherine Porter ◽  
Thu Quach
Keyword(s):  
National Level ◽  
Safety Information ◽  
Health And Safety ◽  
Policy Recommendations ◽  
Safety Issues ◽  
Government Oversight ◽  
Regulatory Perspective ◽  
Nail Salon ◽  
Health And Safety Issues ◽  
Nail Salon Workers

The nail salon sector is growing rapidly. Nail salon workers are predominantly Vietnamese immigrant women who are exposed to numerous harmful chemicals in nail care products. The situation is exacerbated by limited safety information, language barriers to information, and lack of government oversight. This brief discusses the health and safety issues faced by workers at the nexus of environmental and worker justice and the policy recommendations by which to address these issues from a public health and regulatory perspective. Although these policy recommendations pertain to California where the sector is largest, they also have far-reaching implications at the national level.

Fish Hydrolysates: A Regulatory Perspective of Bioactive Peptides

2016 ◽  
Vol 23 (12) ◽  
pp. 1052-1060 ◽  
Author(s):  
Bert Gevaert ◽  
Lieselotte Veryser ◽  
Frederick Verbeke ◽  
Evelien Wynendaele ◽  
Bart Spiegeleer
Keyword(s):  
Bioactive Peptides ◽  
Regulatory Perspective

3D Printing in Pharmaceuticals: Regulatory Perspective

2019 ◽  
Vol 24 (42) ◽  
pp. 5081-5083 ◽  
Author(s):  
Mohd. A. Mirza ◽  
Zeenat Iqbal
Keyword(s):  
New Technologies ◽  
Pharmaceutical Product ◽  
Regulatory Agencies ◽  
Major Research ◽  
Data Bases ◽  
Drug Products ◽  
Regulatory Perspective ◽  
Regulatory Guidelines ◽  
Recent Developments ◽  
Technical Issues

Background: The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medical device and others, has recently forayed into the pharmaceutical industry.Commonly understood as an additive manufacturing technology, 3DP aims at delivering customized drug products and is the most acceptable form of“personalized medicine”. Methods: Data bases and search engines of regulatory agencies like USFDA and EMA have been searched thoroughly for relevant guidelines and approved products. Other portals like PubMed and Google Scholar were also ferreted for any relevant repository of publications are referred to wherever required. Results: So far only one pharmaceutical product has been approved in this category by USFDA and stringent regulatory agencies are working over the drafting of guidelines and technical issues. Major research of this category belongs to the academic domain. Conclusion: It is also implicit to such new technologies that there would be numerous challenges and doubts before these are accepted as safe and efficacious. The situation demands concerted and cautious efforts to bring in foolproof regulatory guidelines which would ultimately lead to the success of this revolutionary technology.

Fraud Risk Awareness and the Likelihood of Audit Enforcement Action

2016 ◽  
Vol 30 (3) ◽  
pp. 379-392 ◽  
Author(s):  
Jared Eutsler ◽  
Erin Burrell Nickell ◽  
Sean W. G. Robb
Keyword(s):  
Financial Reporting ◽  
Financial Distress ◽  
Professional Community ◽  
Securities And Exchange Commission ◽  
Counterfactual Reasoning ◽  
Going Concern ◽  
Enforcement Action ◽  
Fraud Risk ◽  
Regulatory Perspective ◽  
Going Concern Opinion

SYNOPSIS Prior research indicates that issuing a going concern opinion to financially stressed clients generally reduces the risk of litigation against the auditor following a bankruptcy (Kaplan and Williams 2013; Carcello and Palmrose 1994). However, we propose that a going concern report may indicate prior knowledge of financial distress, an important fraud risk factor, and this may have repercussions for the auditor if a fraud is subsequently uncovered. Consistent with counterfactual reasoning theory, experimental research suggests that a documented awareness of fraud risk actually increases the likelihood of litigation against the auditor following a fraud (Reffett 2010). This concern has been echoed by the professional community (AICPA 2004; Golden, Skalak, and Clayton 2006) and may be exacerbated by the current outcome-based regulatory environment (Peecher, Solomon, and Trotman 2013). To examine this issue we review Auditing and Accounting Enforcement Releases (AAERs) issued by the Securities and Exchange Commission (SEC) for alleged financial reporting frauds between 1995 and 2012. Results suggest that going concern report modifications accompanying the last set of fraudulently stated financials are associated with a greater likelihood of enforcement action against the auditor. This finding is consistent with counterfactual reasoning theory and suggests that, from a regulatory perspective, auditors may be penalized for documenting their awareness of fraud risk when financial statements are later determined to be fraudulent.

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